Emergency surgery for hemorrhagic shock caused by a gastrointestinal stromal tumor of the ileum: A case report.

In this report, a case of hemorrhagic shock caused by a gastrointestinal stromal tumor (GIST) of the ileum, which was successfully treated by emergency surgery, is presented. A 67-year-old male patient presented to the Ibaraki Medical Center, Tokyo Medical University (Ami, Japan) in July 18, 2014, with dizziness and blood in the stool. Upper endoscopy and colonoscopy failed to reveal the source of the hemorrhage, although abdominal contrast-enhanced computed tomography revealed extravasation of the contrast medium into the small intestine. The patient developed hemorrhagic shock; thus, double-balloon enteroscopy (DBE) was performed, which revealed a Meckel's diverticulum and a submucosal tumor with excessive bleeding at 60 and 100 cm proximal to the ileocecal valve, respectively. Subsequent emergency partial resection of the ileum, including the tumor and the Meckel's diverticulum, was performed in July 20, 2014. Histological examination of the excised tumor revealed proliferation of spindle-shaped cells, and immunohistochemical staining of the tumor was positive for CD34, KIT and α-smooth muscle actin, but negative for S-100 protein. These immunohistological results supported the diagnosis of GIST of the ileum. The patient had an uneventful recovery and has been monitored at our outpatient clinic for 14 months after surgery. This case demonstrated the efficacy of DBE for the diagnosis of small intestinal bleeding, and immediate emergency surgery should be considered for cases of small intestinal GISTs with excessive bleeding.

Synchronous ovarian metastasis from colorectal cancer: A report of two cases.

Ovarian metastasis of colorectal cancer is relatively rare. The present study reports two cases of synchronous ovarian metastasis from colorectal cancer, which were managed by cytoreductive surgery. In case one, a 60-year-old female patient presented with a multilocular pelvic tumor and ascites. Virtual colonoscopy revealed a mass in the sigmoid colon; however, no tumor cells were identified on histological examination. Ovarian metastasis from sigmoid colon cancer was suspected and adnexectomy was subsequently performed. Histological examination of the excised tumor revealed adenocarcinoma. Immunohistochemical analysis of the resected tumor revealed positive staining for cytokeratin (CK)20 and caudal-type homeobox 2 (CDX2), and negative staining for CK7, estrogen receptor, progesterone receptor and inhibin. The immunohistological results supported the diagnosis of ovarian metastasis from sigmoid colon cancer. In case two, a 56-year-old female patient presented with a multilocular pelvic tumor and ascites. Colonoscopy identified a rectal tumor, and histological examination revealed moderately-differentiated adenocarcinoma, which was confirmed by cytological analysis of ascites. Subsequently, ovarian metastasis from rectal cancer with peritoneal dissemination was diagnosed, and left ovariectomy and transverse colostomy were performed. Histological examination of the excised tumor revealed moderately-differentiated adenocarcinoma, and immunohistochemical investigation revealed positive staining for CK20 and CDX2, but negative staining for CK7. These immunohistological results indicated ovarian metastasis from rectal cancer. Both patients recovered well and are currently undergoing regular follow-up examinations. The observations from the two cases indicate that ovarian metastases of primary colorectal cancer may present as pelvic tumors and, thus, preoperative examination of the gastrointestinal tract is required. Furthermore, even in cases of widespread colorectal cancer metastases, excision of the ovarian tumor is required to establish a histological diagnosis for the selection of appropriate treatments.

Laparoscopic management of an octogenarian adult intussusception caused by an ileal lipoma suspected preoperatively: a case report.

Adult intussusception is rare and usually caused by a tumor acting as the lead point. Therefore, laparotomy should be considered for the treatment. Laparoscopic procedures for use in cases of adult intussusception have been recently reported; however, there is no consensus regarding the safety and efficacy. Here, we describe a successful case of laparoscopic management of an octogenarian adult intussusception caused by an ileal lipoma, which was preoperatively suspected. An 87-year-old male presented with progressive abdominal distention and vomiting. Contrast radiography of the small intestine showed an ileal tumor, and magnetic resonance imaging indicated a target-like mass, consistent with an ileal intussusception. The patient was suspected with an intussusception due to an ileal lipoma, and laparoscopic surgery was performed. An approximately 10-cm-long ileal intussusception with a preceding tumor was present, and partial resection of the ileum, including the tumor, was performed. Macroscopic examination of the excised specimen showed a pedunculated tumor measuring 4.0 × 3.5 × 1.9 cm with an uneven surface, yielding a histological diagnosis of lipoma. The patient had an uneventful recovery and was discharged on postoperative day 8. This successful case showed that laparoscopic surgery can be a useful, safe, and efficacious procedure for adult intussusception, even in octogenarians.

Pre-operative granulocyte/lymphocyte ratio as a predictive marker of post-operative complications in patients with colorectal cancer.

The aim of the present study was to assess the clinical relevance of the pre-operative granulocyte/lymphocyte (G/L) ratio as a predictive marker of post-operative complications in patients with colorectal cancer. In total, 85 patients (59 males and 26 females; mean age, 68.9 years) underwent surgery for colorectal cancer at the Department of Surgery, Ibraki Medical Center, Tokyo Medical University (Ami, Japan), and were divided into post-operative complication and non-complication groups. Clinical data, including age, gender, body mass index, tumor localization, tumor pathological type, cancer staging, surgery time, volume of surgical bleeding, pre-operative G/L ratio and further pre-operative laboratory data, including levels of albumin and C-reactive protein, Glasgow Prognostic Score, white blood cell count and levels of hemoglobin, creatine kinase, lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9 were analyzed between these groups. The total post-operative complication rate was 18.8%. On univariate analysis, the amount of surgical bleeding and the pre-operative G/L ratio were significantly higher in the complication group than in the non-complication group (299.8±361.7 vs. 155.6±268.6 ml, P<0.05; and 6.73±10.38 vs. 3.49±2.78, P<0.05, respectively). Multivariate logistic regression analysis for the risk factors of post-operative complications, determined using univariate analysis, demonstrated that the amount of surgical bleeding and the pre-operative G/L ratio were independent risk factors of post-operative complications in patients with colorectal cancer. In conclusion, the G/L ratio may be a clinically relevant pre-operative predictive marker for post-operative complications.

Long-term survival of a patient with metachronous rectal metastasis from primary cecal cancer who underwent repetitive resection and chemotherapy: a case report.

There are few reported cases of colorectal metastasis from cancers of other organs, particularly other segments of the colon. Here we describe the long-term survival of a 68-year-old male patient with metachronous rectal metastasis from cecal cancer who underwent repetitive resection and chemotherapy. The patient underwent ileocecal resection and hepatectomy for cecal cancer with liver metastasis (T3, N1a, M1a, Stage IVA) in 2006. The patient subsequently underwent splenectomy for splenic metastasis in 2007. In August 2008, barium enema revealed compression of the rectal wall, and abdominal computed tomography (CT) detected a mass along the rectum extending into the pelvis. Rectal metastasis from cecal cancer was suspected and Hartmann's operation with bilateral seminal vesicle dissection was performed. Histological examination of the excised tumor revealed moderately differentiated adenocarcinoma formed in the muscularis propria of the rectum and infiltrating the connective tissue between the seminal vesicle and rectum. However, no tumor was detected in the rectal mucosa or submucosa. These histological findings supported the diagnosis of rectal metastasis from cecal cancer. The patient has been monitored at our clinic for 60 months after surgical removal of the rectal metastasis. The findings from this case should alert oncologists to the potential danger of rectal metastasis from primary colon cancer and the benefits of timely complete resection in terms of improved patient outcomes.

Complete response of lung metastases from rectal cancer to combination first-line therapy of S-1 and irinotecan plus bevacizumab: A case report and review of the literature.

This report presents the case of a 72-year-old male who had undergone abdominoperineal resection following a diagnosis of lower rectal cancer with multiple lung metastases. Pathologically, the resected specimen exhibited advanced rectal cancer with regional lymphoid metastases and was classified as stage IV disease. S-1 and irinotecan (IRIS) plus bevacizumab combination therapy was used to treat the lung metastases following the surgery. S-1 (100 mg/body) was administered orally on days 1-14 of a 28-day cycle, and irinotecan (125 mg/m2) and bevacizumab (7.5 mg/kg) were administered by intravenous infusion on days 1 and 15. Computed tomography revealed a marked decrease in the size of the metastases following three therapeutic courses, and no lung metastases or new lesions were detected following nine therapeutic courses. The response was declared clinically complete. The patient refused additional treatment following nine therapeutic courses, and there was no recurrence 36 months after the final course of therapy. This case demonstrates the efficacy of IRIS plus bevacizumab as a first-line combination therapy against lung metastases of rectal cancer.

Removal of an intra-abdominal desmoplastic small round cell tumor by repetitive debulking surgery: A case report and literature review.

In the current study, a case of recurrent desmoplastic small round cell tumor (DSRCT) is presented, which was successfully treated by repetitive debulking surgery. In May 2010, a 39-year-old male, with a history of surgical resection of intra-abdominal DSRCT, visited the Ibaraki Medical Center, Tokyo Medical University Hospital (Ami, Japan) with severe lower abdominal discomfort. Abdominal computed tomography revealed a large tumor in the pouch of Douglas with a small number of nodules in the abdominal cavity. The recurrent DSRCT was diagnosed and removed via lower anterior resection; however, complete resection was impossible due to multiple peritoneal metastases. One year later, the patient developed pain in the right groin due to the growth of metastasized tumor cells in the groin lymph nodes. The affected lymph nodes were removed utilizing an extra-peritoneal approach. At the time of writing, the patient continues to survive without any symptoms 60 months since the initial surgery. In conclusion, surgical debulking is a significant procedure for relieving patient symptoms as well as improving the survival time of patients with metastatic and recurrent DSRCT.

In patients with colorectal cancer, preoperative serum interleukin-6 level and granulocyte/lymphocyte ratio are clinically relevant biomarkers of long-term cancer progression.

OBJECTIVE: To investigate the clinical significance of the serum inflammatory cytokines and the blood granulocytes/lymphocytes (G/L) ratio in patients with colorectal cancer. METHODS: Forty-six patients underwent surgery for colorectal cancer. The G/L ratio and serum inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor-α (TNF-α), granulocyte colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) were measured before surgery and correlated with the Tumour Node Metastasis classification and overall survival. RESULTS: Serum IL-6 in T3-4, N1-2, M1 cases and cancer stages III-IV sub-groups was significantly higher than in Tis-2, N0, M0 and cancer stages 0-II sub-groups. The G/L ratio, serum M-CSF and TNF-α in T3-4 cases were significantly higher than in Tis-2 cases. Furthermore, the G/L ratio and serum IL-6 showed a significant inverse correlation with the overall survival, while the G/L ratio showed a significant positive correlation with serum IL-6, TNF-α and M-CSF. Multivariate analysis showed that the serum IL-6 level and G/L ratio were independent risk factors for poor prognosis. CONCLUSIONS: In this investigation, a pre-operative high level of serum IL-6 and the G/L ratio appeared to be significant predictive factors for cancer progression and poor prognosis. Accordingly, these variables might be clinically relevant biomarkers in patients with colorectal cancer.

Selectively induced apoptosis in human neutrophils in the presence of oxidative phenoxazines, 2-amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one and 2-aminophenoxazine-3-one, preceded by decrease of intracellular pH, depolarization of the mitochondria, and inhibition of superoxide generation.

The present research investigated the effect of the oxidative phenoxazines, 2-amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one (Phx-1) and 2-amino-phenoxazine-3-one (Phx-3) on apoptosis induction and apoptosis-related early events in human neutrophils. When Phx-1 or Phx-3 was administered to freshly drawn human blood for 18 h, these phenoxazines caused apoptotic cell death morphologically characterized by condensation of the nucleus in neutrophils, without causing it in lymphocytes and monocytes. Apoptosis, which was detectable by microscopic analysis and by using flow-cytometry, occurred significantly in human neutrophils isolated from freshly drawn blood, 6 h after the administration of 50 µM Phx-1 and Phx-3. After 24 h, every isolated neutrophil treated with Phx-1 or Phx-3 fell into apoptosis or lost its morphology, while many of the neutrophils without these phenoxazines remained alive, with normal morphology. Apoptosis-related early events including a decrease in intracellular pH (pHi) and depolarization of the mitochondria occurred in the isolated neutrophils, 30 min and 6 h after the administration of Phx-1 or Phx-3, respectively. Superoxide generation from the isolated neutrophils mimicked by phorbol myristate acetate (PMA) was very markedly inhibited by 100 µM Phx-1 or Phx-3. This result could be explained, in part, by the fact that the insufficient supply of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) was caused by pHi decrease in neutrophils treated with Phx-1 or Phx, because NADPH is necessary for NADPH oxidase responsible for generating superoxide in the cells. The present results suggest that Phx-1 and Phx-3 have the capacity of selectively inducing apoptosis in human neutrophils and that these phenoxazines may be useful as specific drugs to induce apoptotic cell death of human neutrophils and thereby prevent inflammation caused by these phagocytic cells.

Gastric tube perforation after esophagectomy for esophageal cancer.

We searched for cases of perforation of the gastric tube after esophagectomy for esophageal cancer by reviewing the literature. Only 13 cases were found in the English literature, and serious complications were seen in all cases, especially in cases of posterior mediastinal reconstruction. However, in the Japanese literature serious complications were also frequently seen in retrosternal reconstruction. Gastric tubes are at a higher risk of developing an ulcer than the normal stomach, including an ulcer due to Helicobacter pylori infection, insufficient blood supply, gastric stasis, and bile juice regurgitation. H. pylori eradication and acid-suppressive medications are important preventive therapies for ordinary gastric ulcers, but for gastric tube ulcers the effects of such treatments are still controversial. We tried to determine the most appropriate treatment to avoid serious complications in the gastric tubes, but we could not confirm an optimal route because each had advantages and disadvantages. However, at least in cases with severe atrophic gastritis due to H. pylori infection or a history of frequent peptic ulcer treatment, the antesternal route is clearly the best. Many cases of gastric tube ulcers involve no pain, and vagotomy may be one of the reasons for this absence of pain. Therefore, periodic endoscopic examination may be necessary to rule out the presence of an ulcer.

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer.

The coexistence of gastric cancer with duodenal ulcer has been found empirically to be rare, but why it is rare is difficult to explain satisfactorily. To elucidate this question, we carried out a literature review of the subject. The frequency with which the two diseases coexist is 0.1-1.7%, and the main factor associated with both gastric cancer and duodenal ulcer is Helicobacter pylori infection. However, there are marked differences between the disorders of hyperchlorhydria in duodenal ulcer, and hypochlorhydria in gastric cancer. The most acceptable view of the reason for the difference may be that the acquisition of H. pylori infection occurs mainly in childhood, so that the time of acquisition of atrophic gastritis may be the most important, and if atrophic gastritis is not acquired early, high levels of gastric acid may occur, and consequently acute antral gastritis and duodenal ulcer may occur in youth, whereas, in elderly individuals, persistent H. pylori infections and the early appearance of atrophic gastritis may be the causes of low gastric acid, and consequently gastric cancer may occur. In patients with duodenal ulcer, factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and dupA-H. pylori strains may contribute to preventing the early acquisition of atrophic gastritis, while acid-suppressive therapy and vascular endothelial growth factor and other entities may inhibit atrophic gastritis. In contrast, in gastric cancer, factors such as excessive salt intake, acid-suppressive therapy, polymorphisms of inflammatory cytokines, and the homB-H. pylori strain may contribute to the early acquisition of atrophic gastritis, while factors such as NSAIDs; fruits and vegetables; vitamins A, C, and E; and good nutrition may inhibit it.

Overt bone metastasis and bone marrow micrometastasis of early gastric cancer.

Recently we encountered two cases of early gastric cancer (EGC) with bone metastasis after surgery. As they were not accompanied by overt liver, lung, or peritoneal metastasis, we examined the clinical significance of bone metastasis in EGC and its mechanisms by a review of the literature. We found only 10 cases of EGC complicated with overt bone metastasis in the English literature, so we also examined the Japanese reports of such cases. The main histologic type of cases of bone metastasis from EGC was the diffuse type, and there were long intervals between surgery and overt bone metastasis. One reason for such long intervals may have been the tumor dormancy. Two types of dormancy, dynamic and static, and two types of postoperative overt metastases, that of micrometastatic origin (normograde metastatic process) and that of bone marrow origin (retrograde metastatic process), were considered. We speculated that there may be specific routes by which the cancer cells infiltrate the bone marrow directly from EGC or lymph node metastasis. The procedures for diagnosing bone micrometastasis using monoclonal antibodies have recently been improved, but their accuracy rates are still not universally accepted. New, more reliable examinations are required to improve the survival rates of EGC.

The perioperative granulocyte/lymphocyte ratio is a clinically relevant marker of surgical stress in patients with colorectal cancer.

PURPOSE: This study was to assess the clinical relevance of the blood granulocytes to lymphocytes (G/L) ratio as an early marker of surgical stress in patients with colorectal cancer. METHODS: Thirty-three patients with colorectal cancer were prospectively to undergo laparoscopic-assisted (n=12) or open (n=21) surgical resection. Granulocyte and lymphocyte counts were used to calculate the G/L ratios in blood samples from all patients before the operation and post-operatively on days 1, 3 and 7. Additionally, serum inflammatory cytokines, interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were assayed as markers of surgical stress. RESULTS: Seven of 33 patients developed unexpected complications. Serum IL-6 (P<0.0001), G-CSF (P=0.0257), and M-CSF (P<0.0001) were higher on day 1 vs before the operation. Similarly, the G/L ratios were higher on days 1-3 vs before the operation (P<0.0001) and then gradually decreased together with the surgical stress levels. The G/L ratios and the numbers of granulocytes and lymphocytes in the blood showed no correlation with serum IL-1ß or TNF-α. In contrast, the G/L ratios and the numbers of granulocytes in the blood showed significant correlation with IL-6 (Rs=0.710, P<0.0001, Rs=0.653, P<0.0001, respectively), with G-CSF (Rs=0.626, P<0.0001, Rs=0.578, P<0.0001), with M-CSF (Rs=0.470, P<0.0001, Rs=0.372, P<0.0001). However, the number of lymphocytes showed inverse correlation with IL-6 (Rs=-0.493, P<0.0001), G-CSF (Rs=-0.440, P<0.0001) and M-SCF (Rs=-0.443, P<0.0001). CONCLUSION: The G/L ratio appears to be a simple and clinically relevant parameter for the assessment of perioperative stress in patients undergoing colorectal surgery.

Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients.

BACKGROUND AND OBJECTIVES: Th2-dominant immunity and high neutrophil/lymphocyte ratios (NLRs) have been reported to reflect tumor progression, and so we examined whether the Th1/Th2 ratio and NLR can act as prognostic indicators or not. METHODS: Peripheral blood samples were taken within 1 week before and 14 postoperative days after curative gastrectomy using 157 gastric cancer cases for the measurement of both ratios. The proportions of Th1 cells (interferon γ-producing CD4 T cells), Th2 cells (interleukin-4-producing CD4 T cells) were counted by two-color flow cytometry analysis. RESULTS: There were significant differences in 5-year survival both between the high and low Th1/Th2 ratio groups, and between the high and low NLR groups. The pattern classifications before and after surgery in the Th1/Th2 ratio showed strongly significant differences in 5-year survival. NLR was especially influenced by tumor size, and there was a negative linear correlation between the two ratios before surgery. CONCLUSIONS: The Th1/Th2 ratio may be a good prognostic indicator and may also be a promising marker for estimating the effectiveness of surgery. NLR may also be a good prognostic indicator and may be a valid marker of tumor recurrence, and it appeared that some interaction between lymphocytes and neutrophils had occurred.

It is possible that tumour-infiltrating granulocytes promote tumour progression.

Several lines of evidence indicate that tumour-infiltrating granulocytes (TIGs) promote tumour growth and progression. However, the prognostic significance of TIGs, the relationship between TIGs and Fas ligand (FasL) expressed on tumour cells remains unclear and warrants investigation. Using immunnostaining, we retrospectively investigated TIGs and FasL in 130 tissue specimens from gastric carcinoma. We analyzed the correlation among these markers, their association with clinicopathologic features and prognosis. The number of TIGs was significantly associated with FasL-expression (P=0.002). Further, TIGs were significantly associated with depth of tumour invasion, lymph node metastasis and tumour stage. Calculating the prognostic relevance, in multivariate analysis, TIGs [relative risk (RR)=1.014; 95% CI=1.002-1.027; P=0.015] and tumour stage were statistically significant factors for survival. Our results suggest that TIGs are conveniently measured by the immunostaining method, and possibly serve as an independent factor of prognosis in patients with gastric carcinoma. This is based on the fact that TIGs were significantly associated with tumour stage and shorter survival time.

The distribution and intracellular location of Fas and Fas Ligand following gastric carcinogenesis: Fas Ligand expressing gastric carcinoma cells can inhibit local immune response.

Previous reports indicated that Fas Ligand (FasL) in gastric carcinoma might support tumour cells to evade host immune attack. However, the mechanism induced by the Fas/FasL system has not yet been described on the basis of comparison of normal and malignant tissues in terms of the features of regional location of Fas and FasL. By using immunostaining methods, we studied the distribution and regional location of Fas and FasL in gastric epithelial cells (GECs), gastric carcinoma cells (GCCs), normal gastric stroma-infiltrating lymphoid cells (NGILs) and tumour-infiltrating lymphoid cells (TILs) in 59 tissue specimens of human gastric carcinoma. The expression of Fas within the entire GECs was higher than that in all GCCs (P < 0.0001); however, the expression of Fas in NGILs was lower than that in TILs (P < 0.0001). The expression of FasL showed no significant difference between GECs and GCCs, or between NGILs and TILs. When we analyzed the Fas/FasL expression on cytomembrane (CM) in GECs and GCCs, Fas-in-CM was detected in 79.4% and 33.33% (P < 0.05), compared with 3.03% and 56.67%, respectively, for FasL-in-CM (P < 0.001). Our results suggest that there is indeed a possible mechanism to assist cancer cells to evade host immune attack, and this mechanism depends on the dynamic state of Fas/FasL expression, that is, Fas showed a tendency to be expressed within the cells, whereas FasL showed a tendency to be expressed on the cell membrane following carcinogenesis.

Histological factors contributing to a high risk of recurrence of submucosal invasive cancer (pT1) of the colon and rectum after endoscopic therapy.

We analyzed the histological high-risk factors for recurrence of submucosal invasive carcinomas (pT1) of the colon and rectum after endoscopic therapy, examining pT1 cancers treated primarily by endoscopic resection within a 23-year period. We compared recurrent and nonrecurrent cancers, evaluating the following "highrisk factors" of the primary lesion: massive invasion, a surgical margin<2 mm but negativity for cancer in the cut end, poorly differentiated adenocarcinoma (PD) (G3), undifferentiated carcinoma (G4), and/or positive angiolymphatic invasion. The following histological factors were defined as predictive of a low risk: minimum invasion, a surgical margin>2 mm, well or moderately differentiated adenocarcinoma (G1, G2), and no evidence of angiolymphatic invasion. We analyzed the records of 37 patients with pT1 cancers, including 15 with high-risk factors who underwent subsequent resection. Local recurrence with or without liver metastases developed in 4 of these 15 patients. The histological type was PD in three (75%) of the four recurrent lesions. All four (100%) lesions showed a desmoplastic response (DR). Only 1 (9%) of the 11 patients without recurrence after subsequent surgery had a lesion with a small component of PD, and only three (27%) lesions showed a mild DR. We concluded that endoscopic therapy is inadequate for pT1 cancers with a histological PD component, and/or a DR in the cancer stroma.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression: Its clinical applications.

Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x105 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x105 cells) and E, F, G and H (1x106 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Prognostic significance of immunohistochemically detected blood and lymphatic vessel invasion in colorectal carcinoma: its impact on prognosis.

BACKGROUND: The prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI. METHODS: By immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI. RESULTS: The use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival. CONCLUSIONS: Our results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.

[Evaluation of CA72-4 as a tumor marker in patients with gastric cancer].

The clinical efficacy of CA72-4 for gastric cancer was studied in comparison with CEA and CA19-9. These 3 markers were examined simultaneously, preoperatively in 156 cases of gastric cancer. The positive rate of CA72-4 was higher than of CA19-9 and was equivalent to CEA. There was no significant difference between differentiated and undifferentiated carcinoma in these 3 markers. However, the positive rates of CEA and CA72-4 were significant higher in the cases with lymph node metastasis and curative grade B, C. The combination assay of CEA and CA72-4 was valuable because the tumor markers were considered to be independent of each other. Cases positive for both CEA and CA72-4 simultaneous were significantly more frequent among the cases with lymph node metastasis and in the serosa-invasive cases. In conclusion, CA72-4 is more important than CA19-9 as a tumor marker in gastric cancer patients.